TMG (Tri-methyl-glycine) / SAMe

An extract from sugar beets and also known as anhydrous Betaine, TMG is a natural polysaccharide and a good source of methyl groups that promotes healthier levels of the powerful pro-oxidant and free radical generator homocysteine. Homocysteine is a toxic end product of the metabolism (methylation) of methionine (an essential amino acid) and is now known to be a leading cause of heart and artery disease.

Multiple studies have demonstrated that medium to high levels of plasma homocysteine are associated with increased risk of heart disease, cerebrovascular disease and peripheral artery disease. In one study, daily treatment with TMG, folic acid and choline normalized homocysteine levels in 17 of 19 patients. Arteriosclerosis[/glossary] and Thrombosis 13(9): pp.1253-60, 1993]

Along with cofactors such as vitamins B6, B12 and Folic Acid, TMG is part of a chemical contingent in the body that works against cancer, heart and neurological diseases, and nearly every age-related disorder.

TMG is a versatile nutrient and provides an intermediary metabolite that can enable a person or animal to function at more optimum mental and physical levels. It aids the body in overcoming a number of adverse health conditions, and is an intricate part of human metabolism. DMG (TMG’s metabolite) has been used as a nutritional supplement for over 25 years. In a broad sense, TMG protects the body from many forms of physical, metabolic and environmental stress.

Applications include
Immune modulation: Improves antibody response, enhances B- and T-cell function, and regulates cytokines.
Viral/bacterial infections: Enhances immune response.
Cardiovascular: Reduces cholesterol and triglyceride levels, helps eliminate hypoxia, improves coronary circulation, decreases angina pain.
Athletic performance: Enhances endurance, improves oxygen utilization, reduces lactic acid buildup, improves muscle recovery.
Autism/epilepsy: Improves verbal communication/social interaction/lethargy, may reduce seizures Chronic fatigue syndrome: Greater mental alertness and energy, improves immune dysfunction.
Melanoma: Anti-tumor activity, prevents metastasis.
Lupus (SLE): Reduces antinuclear antibodies, modulates cytokine production.

In the liver, TMG transfers one of its three methyl groups to homocysteine, which is then converted into the useful amino acid methionine.

When methylation is working properly, homocysteine is quickly converted back to methionine which is then converted to SAMe (S-adenosylmethionine), which protects the liver and is a natural antidepressant. SAMe then acts as a methyl donor for DNA: when attached to DNA, methyl groups appear protective, preventing mutated genes from expressing themselves. It may improve health, reduce the risk of genetically induced cancers, and slow cellular aging. Factors that decrease methylation include smoking, alcohol consumption, high fat diets and birth control pills.

TMG supplementation may sometimes produce hyperactivity in autistic children. Folic acid appears to help neutralize this effect at one or two 800mcg tablets.

The usual TMG dose is 500 to 1,000mg per day – roughly equivalent to what a diet high in broccoli, spinach or beets would provide.

If you are using SAMe, though more expensive, try taking 400mg BID. If symptoms fail to improve after three weeks, try increasing your dose to 400mg TID. If symptoms lessen with 400mg BID, you can try to lower the dose to 200mg BID.

NOTE: An inexpensive variety is Betaine HCL which acts as a stomach acidifier and is not practical due to stomach irritation at the doses required to enhance methylation metabolism.


TMG (Tri-methyl-glycine) / SAMe can help with the following


Addictions / Addictive Tendencies

TMG or SAMe may be especially useful in treating depression associated with drug withdrawal.


Parkinson's Disease / Risk

The compound 5-adenosylmethionine (SAMe), potentially produced through the demethylation of TMG, has been shown to improve Parkinson’s disease.





A four-year clinical evaluation of DMG (or TMG) by Mitchell Pries, MD of Palmdale, California has confirmed Soviet findings. In trials involving the administration of DMG at 125mg bid to over 400 cardiovascular patients, Dr. Pries reported major improvements in several areas including arrhythmias. This dose is low, and a more rapid response may be possible at higher doses.


Environment / Toxicity  



Histadelia (Histamine High)

One thing that is absolutely certain is that methionine and/or SAMe usually harm low-histamine (overmethylated persons)….. But are wonderful for high-histamine (undermethylated) persons. The reverse in true for histadelic (undermethylated) persons, who thrive on methionine, SAMe, Ca and Mg….. But get much worse if they take folates & B-12 which can increase methyl trapping. [Willam Walsh, Ph.D., past senior scientist, Pfeiffer Treatment Center]


Low Progesterone or Estrogen Dominance

TMG converts to S-adenosyl methionine (SAMe, an activated form of methionine) in the body. SAMe assists in the breakdown of estrogens.


Low Adrenal Function / Adrenal Insufficiency

The adrenal gland uses nutrients such as TMG (betaine), tyrosine, vitamins B5, B6 and C to maintain function and produce its hormones.


Histapenia (Histamine Low)

DMG and TMG (dimethyl and trimethylglycine) or SAMe may cause adverse reactions in some.

The Immune System  


Lab Values  




The compound 5-adenosylmethionine (SAMe), potentially produced through the demethylation of TMG, has been shown to alleviate depression.

Six weeks of oral SAMe at 1600mg per day improved depression scores similarly to oral imipramine at 150mg per day in a comparison study of 281 patients with major depression. Fewer adverse effects were observed in the patients treated

with SAMe. [Am J Clin Nutr 2002;76(5): pp.1172S-6S]


Tendency Toward Postpartum Depression

TMG or SAMe may be superior to methionine for the treatment of depression. It may be especially useful in treating postpartum depression and depression associated with drug withdrawal.


Bipolar Disorder, Manic-Depressive

SAMe can cause a person with bipolar depression (a history of irritability, temper outbursts and swings in mood, energy level and need for sleep) to become manic. The bipolar form of depression is very common and is often misdiagnosed as plain depression. People should not use SAMe or TMG without first having a thorough evaluation to rule out bipolar disorder.


Gilbert's Syndrome

Methionine, administered as SAM, resulted in a significant decreases in serum bilirubin in patients with Gilbert’s syndrome in a clinical study. SAM has been used with favorable results in a variety of other chronic liver diseases. TMG converts to SAMe while being considerably less expensive. TMG can be helpful in treating Gilbert’s syndrome because it activates several Phase II pathways.





TMG, administered as S-adenosyl-methionine (SAMe), was shown to be superior to ibuprofen (Motrin) in the treatment of osteoarthritis in a double-blind clinical trial. The positive effect in this trial is consistent with several other clinical studies.

Nervous System  

Seizure Disorder

TMG has been noted to reduce seizure activity in some individuals.

Organ Health  



Fatty Liver

The therapeutic indication for SAMe in intrahepatic cholestasis and alcoholic liver disease is based on it’s anti-steatotic, anti-inflammatory, anti-oxidant and anti-fibrotic properties. An oral dose of 600 mg/day or intramuscular administration of 50 to 100 mg/day have shown therapuetic benefit regarding biochemical, histological, and echographic parameters of liver steatosis.





May do some good
Likely to help
Highly recommended
May have adverse consequences
Reasonably likely to cause problems



Water deficient.


Tri-methyl-glycine. After supplying a methyl group, TMG becomes di-methyl-glycine. DMG, a natural component of animal and plant metabolism, positively influences the immune response in laboratory animals and humans and boosts physical and mental performance.

Free Radical

A free radical is an atom or group of atoms that has at least one unpaired electron. Because another element can easily pick up this free electron and cause a chemical reaction, these free radicals can effect dramatic and destructive changes in the body. Free radicals are activated in heated and rancid oils and by radiation in the atmosphere, among other things.


The chemical processes of living cells in which energy is produced in order to replace and repair tissues and maintain a healthy body. Responsible for the production of energy, biosynthesis of important substances, and degradation of various compounds.


Essential amino acid. Dietary source of sulfur and methyl groups. Important for proper growth in infants, nitrogen balance in adults, healthy nails and skin and the synthesis of taurine, cysteine, phosphatidylcholine (lecithin), bile, carnitine and endorphins. It is an antioxidant nutrient and lipotropic agent which promotes the physiological utilization of fat.

Amino Acid

An organic acid containing nitrogen chemical building blocks that aid in the production of protein in the body. Eight of the twenty-two known amino acids are considered "essential," and must be obtained from dietary sources because the body can not synthesize them.

Folic Acid

A B-complex vitamin that functions along with vitamin B-12 and vitamin C in the utilization of proteins. It has an essential role in the formation of heme (the iron containing protein in hemoglobin necessary for the formation of red blood cells) and DNA. Folic acid is essential during pregnancy to prevent neural tubular defects in the developing fetus.


A lipotropic substance sometimes included in the vitamin B complex as essential for the metabolism of fats in the body. Precursor to acetylcholine, a major neurotransmitter in the brain. Choline prevents the deposition of fats in the liver and facilitates the movement of fats into the cells. Deficiency leads to cirrhosis of the liver.


Formation of blood clots causing vascular obstruction.


A substance that acts with another substance to bring about certain effects, often a coenzyme.

Vitamin B6

Influences many body functions including regulating blood glucose levels, manufacturing hemoglobin and aiding the utilization of protein, carbohydrates and fats. It also aids in the function of the nervous system.


Vitamin B-12. Essential for normal growth and functioning of all body cells, especially those of bone marrow (red blood cell formation), gastrointestinal tract and nervous system, it prevents pernicious anemia and plays a crucial part in the reproduction of every cell of the body i.e. synthesis of genetic material (DNA).


Refers to the various types of malignant neoplasms that contain cells growing out of control and invading adjacent tissues, which may metastasize to distant tissues.


Any product (foodstuff, intermediate, waste product) of metabolism.


A type of serum protein (globulin) synthesized by white blood cells of the lymphoid type in response to an antigenic (foreign substance) stimulus. Antibodies are complex substances formed to neutralize or destroy these antigens in the blood. Antibody activity normally fights infection but can be damaging in allergies and a group of diseases that are called autoimmune diseases.


T cells are lymphocytes that are produced in the bone marrow and mature in the thymus. T cells are responsible for mediating the second branch of the immune system called "cellular immune response." T cells can live for months to years. This lymphocyte population is defined by the presence of a rearranged T-cell receptor.


Cytokines are chemical messengers that control immune responses. They are secreted by white blood cells, T cells, epithelial cells and some other body cells. There are at least 17 different kinds of interleuken and 3 classes of interferon called alpha, beta and gamma and various subsets. Interleukens and interferons are called “cytokines” and there are two general groupings, Th1 and Th2. Th1 (T-cell Helper type 1) promote cell-mediated immunity (CMI) while Th2 (T-cell Helper type 2) induce humoral immunity (antibodies).


Pertaining to the heart and blood vessels.


A waxy, fat-like substance manufactured in the liver and found in all tissues, it facilitates the transport and absorption of fatty acids. In foods, only animal products contain cholesterol. An excess of cholesterol in the bloodstream can contribute to the development of atherosclerosis.


The main form of fat found in foods and the human body. Containing three fatty acids and one unit of glycerol, triglycerides are stored in adipose cells in the body, which, when broken down, release fatty acids into the blood. Triglycerides are fat storage molecules and are the major lipid component of the diet.


Angina pectoris. Severe, restricting chest pain with sensations of suffocation caused by temporary reduction of oxygen to the heart muscle through narrowed diseased coronary arteries.


Chronic brain disorder associated with some seizures and, typically, alteration of consciousness.


While there are over 40 types of seizure, most are classed as either partial seizures which occur when the excessive electrical activity in the brain is limited to one area or generalized seizures which occur when the excessive electrical activity in the brain encompasses the entire organ. Although there is a wide range of signs, they mainly include such things as falling to the ground; muscle stiffening; jerking and twitching; loss of consciousness; an empty stare; rapid chewing/blinking/breathing. Usually lasting from between a couple of seconds and several minutes, recovery may be immediate or take up to several days.

Chronic Fatigue Syndrome

CFS (Chronic Fatigue Syndrome) is a disorder of unknown cause that lasts for prolonged periods and causes extreme and debilitating exhaustion as well as a wide range of other symptoms such as fever, headache, muscle ache and joint pain, often resembling flu and other viral infections. Also known as Chronic Fatigue and Immune Dysfunction Syndrome (CFIDS), Chronic Epstein-Barr Virus (CEBV), Myalgic Encephalomyelitis (ME), "Yuppy Flu" and other names, it is frequently misdiagnosed as hypochondria, psychosomatic illness, or depression, because routine medical tests do not detect any problems.


A life-threatening type of skin cancer that occurs in the cells (melanocytes) that produce melanin, the pigment found in skin, hair, and the iris of the eyes.


Deoxyribonucleic acid, the large molecule that is the main carrier of genetic information in cells. DNA is found mainly in the chromosomes of cells.


(mcg): 1/1,000 of a milligram in weight.


(mg): 1/1,000 of a gram by weight.


Twice per day.


Three times a day.

Hydrochloric Acid

(HCl): An inorganic acidic compound, excreted by the stomach, that aids in digestion.


A hollow, muscular, J-shaped pouch located in the upper part of the abdomen to the left of the midline. The upper end (fundus) is large and dome-shaped; the area just below the fundus is called the body of the stomach. The fundus and the body are often referred to as the cardiac portion of the stomach. The lower (pyloric) portion curves downward and to the right and includes the antrum and the pylorus. The function of the stomach is to begin digestion by physically breaking down food received from the esophagus. The tissues of the stomach wall are composed of three types of muscle fibers: circular, longitudinal and oblique. These fibers create structural elasticity and contractibility, both of which are needed for digestion. The stomach mucosa contains cells which secrete hydrochloric acid and this in turn activates the other gastric enzymes pepsin and rennin. To protect itself from being destroyed by its own enzymes, the stomach’s mucous lining must constantly regenerate itself.

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